Study summary · research use only
Centrally Acting Agents for Obesity: Past, Present, and Future
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This narrative review describes the history and pharmacology of centrally acting drugs for obesity in humans, from early amphetamines through current and investigational agents. It describes phentermine/topiramate as acting through multiple neurotransmitter pathways to reduce appetite, and the combination of bupropion/naltrexone, in which naltrexone blocks a feedback inhibitory circuit of bupropion. It also discusses lorcaserin, described as a selective agonist of a serotonin receptor that regulates food intake, and the GLP-1 receptor agonist liraglutide. Compounds in development discussed include tesofensine, described as a triple reuptake inhibitor in Phase III trials for obesity; semaglutide, an oral GLP-1 analog approved for diabetes and in trials for obesity; and setmelanotide, a melanocortin-4 receptor agonist in early development. The review anticipates future obesity drug development moving toward new central and peripheral targets.
Abstract
For many years, obesity was believed to be a condition of overeating that could be resolved through counseling and short-term drug treatment. Obesity was not recognized as a chronic disease until 1985 by the scientific community, and 2013 by the medical community. Pharmacotherapy for obesity has advanced remarkably since the first class of drugs, amphetamines, were approved for short-term use. Most amphetamines were removed from the obesity market due to adverse events and potential for addiction, and it became apparent that obesity pharmacotherapies were needed that could safely be administered over the long term. This review of central nervous system (CNS) acting anti-obesity drugs evaluates current therapies such as phentermine/topiramate, which act through multiple neurotransmitter pathways to reduce appetite. In the synergistic mechanism of bupropion/naltrexone, naltrexone blocks the feed-back inhibitory circuit of bupropion to give greater weight loss. Lorcaserin, a selective agonist of a serotonin receptor that regulates food intake, and the glucagon-like-peptide-1 (GLP-1) receptor agonist liraglutide are reviewed. Future drugs include tesofensine, a potent triple reuptake inhibitor in Phase III trials for obesity, and semaglutide, an oral GLP-1 analog approved for diabetes and currently in trials for obesity. Another potential new pharmacotherapy, setmelanotide, is a melanocortin-4 receptor agonist, which is still in an early stage of development. As our understanding of the communication between the CNS, gut, adipose tissue, and other organs evolves, it is anticipated that obesity drug development will move toward new centrally acting combinations and then to drugs acting on peripheral target tissues.
pepmg summarizes the peer-reviewed literature and links to every source — it sells nothing, ships nothing, and gives no medical, dosing, or human-use guidance. Don't just trust this summary: follow the citation to its source and read it yourself. Research use only.